1. Field of the Invention
The present invention relates to a novel method for producing an optically active β-amino acid very important as intermediate for production of medicines, agricultural chemicals and physiologically active substances, and very useful, for example, as intermediate for the synthesis of antibiotics.
2. Description of the Related Art
Up to now, several methods for preparing optically active β-amino acids have been known; for example, 1) the one in which the corresponding racemic β-amino acid is firstly prepared, followed by optical resolution of the product using an optically active resolution agent or an enzyme, or 2) the one by means of asymmetric synthesis, and so on.
Examples of the method 1) include the technique in which an enzyme is used for optical resolution of the racemate, namely, for example, the one where penicillin acylase is used for hydrolyzing selectively one of the optical isomers of the N-phenylacetyl derivative of a β-amino acid (Synlett, 1993, 339). And, known examples of the method 2) include those techniques described in, for example, “Enantioselective Synthesis of β-Amino Acids”, edited by Eusebio Juaristi, Wiley-VCH, New York.
However, a technique using the method 1), in which an optically active resolution agent is used for optical resolution of the racemate, requires more than one mole equivalent of the resolution agent to the β-amino acid to be resolved, and, in addition, troublesome operations such as crystallization, separation, and purification for obtaining an optically active β-amino acid. And, a technique using the method 1), in which an enzyme is used for resolving a racemate, has drawbacks in that the substrate to which the method is applicable and the absolute configuration of the product β-amino acids are restricted to the specific ones, although the technique gives β-amino acids of relatively high optical purities.
The method 2), which adopts the technique of asymmetric synthesis, has the problem to require an expensive optically active compound as the reagent in an amount more than stoichiometric to the racemate to be resolved.
As solutions to these problems, several methods for preparing β-amino acids by the catalytic asymmetric synthesis are known.
Examples of the known catalytic asymmetric synthesis include (1) the asymmetric addition of silyl-enol-ethers to imines by using optically active zirconium Lewis-acid catalysts (Chemistry Today (GENDAI KAGAKU), 2000, 348, 34); (2) the catalytic asymmetric hydrogenation of β-acylamino-α,β-unsaturated esters (WO99/59721, Tetrahedron: Asymmetry 1991, 2, 543, Tetrahedron Lett., 19, 1119 (1978) and J. Am. Chem. Soc., 124, 4952 (2002)).
However, all the catalytic asymmetric syntheses mentioned above require protecting the nitrogen atom in the optically active compound with a substituent or a protecting group which induces appropriate asymmetry, although the amount of the optically active compound required for carrying out the catalytic asymmetric synthesis is small. Furthermore, the products obtained by the catalytic asymmetric syntheses still have the protecting groups on the nitrogen atoms and procedures for deprotection and so on are needed to get the desired optically active β-amino acids. This may cause another problem to deprotect under conditions where only the protecting group is removed.
The catalytic asymmetric hydrogenation of the method (2) mentioned above requires introduction of a protecting group such as an acyl group and so on at the amino group in the starting compound and, furthermore, in the step of introduction of the protecting group such as an acyl group to the starting β-amino-α,β-unsaturated esters, either E- or Z-isomer of the ester has to be produced selectively, or after introducing an acyl group, the β-acylamino-α,β-unsaturated ester obtained has to be purified.
Furthermore, the optically active β-amino acids obtained by the catalytic asymmetric hydrogenation of β-acylamino-α,β-unsaturated esters are still in the form protected at the amino group with, for example, an acyl group. Therefore, the acyl group has to be removed under conditions where, for example, the ester group is not hydrolyzed. These are problems in the known methods.
Thus, developing a generally applicable and highly efficient catalytic method for the production of an optically active β-amino acid, which does not require troublesome procedure such as introduction of a protecting group in the starting compound and deprotection of the protecting group for obtaining the objective optically active β-amino acid, has been eagerly longed for.
JP-A-H10-231286 discloses a method for producing 2-phenyl-2-(2′-piperidinyl)acetic acid ester derivatives by catalytic asymmetric hydrogenation of 2-phenyl-2-(2′-piperidinylidene)acetic acid derivatives having a secondary amino group.
The starting materials, 2-phenyl-2-(2′-piperidinylidene)acetic acid ester derivatives, mentioned above have, however, each a secondary amino group which is also constituting a cyclic structure. No method for obtaining optically active β-amino acids in high optical purities by catalytic asymmetric hydrogenation of β-amino-α,β-unsaturated esters having a primary amino group, namely, an amino group having no substituent on the nitrogen atom, has been known yet.